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Ji-Hoon Lee, MinA Park, Myung Jae Park, Yong Suk Jo Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, KyungHee University Hospital, Seoul, Republic of Korea Background and objective: Although depression is considered one of the comorbidities of COPD, the clinical characteristics of depression in patients with early COPD remain unknown. We aimed to use national-level data to identify the clinical features and risk factors of depression in patients with early COPD. Methods: We examined 7,550 subjects who were registered in the Korean National Health and Nutrition Examination Survey database of 2014 because that was the only year in which the Patient Health Questionnaire-9 for depression status was administered. Spirometry was used to identify patients with COPD whose forced expiratory volume in 1 second was 50% or more, and these patients were included in the analysis. Results: Of the 211 subjects with early COPD, 14.2% also had depression, whereas 85.8% did not. The patients with depression were predominantly living alone and had a greater prevalence of diabetes compared with the patients without depression. The overall quality of life of the subjects with depression was lower than that of those without depression, and only the quality of life index correlated significantly with depression severity. In the multivariate regression analysis, female sex (adjusted OR, 1.79; 95% CI, 1.38–2.31; p

Abstract Background How novel phenotypes originate from conserved genes, processes, and tissues remains a major question in biology. Research that sets out to answer this question often focuses on the conserved genes and processes involved, an approach that explicitly excludes the impact of genetic elements that may be classified as clade-specific, even though many of these genes are known to be important for many novel, or clade-restricted, phenotypes. This is especially true for understudied phyla such as mollusks, where limited genomic and functional biology resources for members of this phylum have long hindered assessments of genetic homology and function. To address this gap, we constructed a chromosome-level genome for the gastropod Berghia stephanieae (Valdés, 2005) to investigate the expression of clade-specific genes across both novel and conserved tissue types in this species. Results The final assembled and filtered Berghia genome is comparable to other high-quality mollusk genomes in terms of size (1.05 Gb) and number of predicted genes (24,960 genes) and is highly contiguous. The proportion of upregulated, clade-specific genes varied across tissues, but with no clear trend between the proportion of clade-specific genes and the novelty of the tissue. However, more complex tissue like the brain had the highest total number of upregulated, clade-specific genes, though the ratio of upregulated clade-specific genes to the total number of upregulated genes was low. Conclusions Our results, when combined with previous research on the impact of novel genes on phenotypic evolution, highlight the fact that the complexity of the novel tissue or behavior, the type of novelty, and the developmental timing of evolutionary modifications will all influence how novel and conserved genes interact to generate diversity.

Study Design A prospective longitudinal cohort study. Purpose To evaluate the efficacy of two different techniques of transforaminal epidural steroid injection (TFESI) with contrast and without contrast in treating lumbar radiculopathy. Overview of Literature Epidural injections are one of the most frequently used nonsurgical treatment options for managing lumbar radiculopathy. This study aims to simplify the TFESI technique, which is effective and requires less effort to replicate. Methods We collected data on 118 patients who underwent TFESI without contrast versus TFESI with contrast for lumbar radiculopathy. The pain was evaluated using a Numerical Rating Scale (NRS) for pain at 5 minutes, 2 hours, 2 weeks, and 2 months. The functional status was assessed using the Oswestry Disability Index (ODI) score. The operation time and fluoroscopic dosage were also measured using this score. Results Two groups of patients with radiculopathy were studied, comprising of 56 patients in the non-contrast group (NC group) and 62 patients in the contrast group (C group). There was a significant decrease in pain, as evaluated by NRS, in the C group compared to the NC group at 5 minutes post-procedure (3.39±1.54 vs. 3.86±0.72, with a p-value of 0.039). There was no significant difference in NRS scores at 2 hours, 2 weeks, and 2 months, as well as in ODI scores. The operation time and fluoroscopic dosage were lower in the group without contrast compared to the contrast group, with 12.58±3.30 minutes per level vs. 16.70±5.94 minutes per level (p

OBJECTIVE: To study whether allergy consultation and penicillin allergy skin testing affects the selection of antibacterial prophylaxis perioperatively in surgical patients with history of allergy to penicillin (HOAP). PATIENTS AND METHODS: From January 1 through June 30, 2004, we compared 2 different models of practice at our institution. At the Preoperative Evaluation Clinic (POEC), all patients with HOAP are evaluated by an allergist and undergo skin testing for allergy to penicillin. At other (non-POEC) preoperative evaluation settings (OPES), patients with HOAP do not undergo allergy consultation and penicillin skin testing before surgery. Of the 4889 patients screened at the POEC during the study period, 412 consecutive patients with HOAP were included in the study. Of the 416 patients screened at OPES, 69 consecutive patients with HOAP were studied. Logistic regression was used to assess whether allergy consultation was associated with the choice of antibiotic for antibacterial prophylaxis perioperatively, after adjusting for age, sex, and type of surgery. RESULTS: Perioperative cephalosporin use was greater among patients screened at POEC vs those screened at OPES (70% vs 39%, P<.001 unadjusted; P=.04 adjusted for age, sex, and type of surgery). Vancomycin use was lower for patients screened at POEC vs those screened at OPES (10% vs 28%, P<.001 unadjusted; P=.03 adjusted). CONCLUSION: For patients with HOAP, evaluation at the POEC was associated with increased use of cephalosporin and decreased use of vancomycin. [ABSTRACT FROM AUTHOR]

Among patients with a reported history of penicillin allergy, 80% to 90% have no evidence of IgE antibodies to penicillin on skin testing and thus avoid penicillin unnecessarily. Moreover, 97% to 99% of such patients with a penicillin skin test negative to the major and minor determinants can tolerate penicillin without risk of an immediate-type hypersensitivity reaction. A penicillin skin test is valuable for evaluating penicillin allergy in patients who need penicillin or cephalosporin. Assessment of sensitivities to penicillin is important to reduce the unnecessary use of antimicrobial agents such as vancomycin. We review the role of penicillin skin testing for evaluating penicillin allergy and the use of cephalosporin in patients with a history of penicillin allergy. [ABSTRACT FROM AUTHOR]

Objective: The aim of this experiment was to investigate the effect and the mechanism of Geumgoeshingi-whan (GGSGW) Pharmacopuncture at the acupoint GV 4 on the blood pressure in spontaneously hypertensive rats (SHR). Methods: SHR were injected with normal saline solution (Control-SHR group)or GGSGW Pharmacopuncture (GGSGW-SHR group) at the acupoint GV 4. The systolic arterial blood pressure and renal parameters were measured for two weeks. Results: The systolic arterial blood pressure was decreased significantly after GGSGW Pharmacopuncture at the acupoint GV 4 in SHR, followed by a significant rise in creatine clearance. The plasma levels of aldosterone were decreased significantly after GGSGW Pharmacopunctureas were the plasma levels of atrial natriuretic peptide (ANP). Conclusion: These results suggest that the blood pressure was decreased significantly after GGSGW Pharmacopuncture at the acupoint GV 4 in SHR and that the depressor response of the blood pressure was related to decreases in the plasma levels of aldosterone and ANP.

Objective: This study was performed to analyze the singledose toxicity of Aconitum kusnezoffii Reichb. pharmacopuncture (AKRP). Methods: All experiments were conducted at the Korea Testing & Research Institute (KTRI), an institute authorized to perform non-clinical studies, under the regulations of Good Laboratory Practice (GLP). Twenty (20) Sprague-Dawley rats were chosen for the pilot study. The animals were divided into four groups of five animals per group: group 1 (G1) being the control group with each animal receiving an injection of 0.3 ml of saline and groups 2, 3, and 4 (G2, G3, and G4) being the experimental groups with each animal receiving an injection of 0.1, 0.2 or 0.3 ml of AKRP, respectively. This study was conducted with the approval of the Institutional Animal Ethics Committee. Results: No deaths occurred in any of the 4 groups, and the LD50 of AKRP administered via IV was higher than 1.77 ml/kg. Some changes in the weights of the male rates were observed between the control group and the experimental groups, but no significant differences were noted in the weights of the female rats. To check for abnormalities in organs and tissues, we stained representative sections of each specified organ with Hematoxylin & Eosin for light microscopic examination. The results showed no significant differences in any of the organs or tissues. Conclusions: The above findings suggest that Aconitum kusnezoffii Reichb. pharmacopuncture is a relatively safe treatment. Further studies on the subject should be conducted to yield more concrete evidence.

The spontaneous regression of herniated cervical discs is not a well-established phenomenon. However, we encountered a case of a spontaneous regression of a severe radiculopathic herniated cervical disc that was treated with acupuncture, pharmacopuncture, and herb medicine. The symptoms were improved within 12 months of treatment. Magnetic resonance imaging (MRI) conducted at that time revealed marked regression of the herniated disc. This case provides an additional example of spontaneous regression of a herniated cervical disc documented by MRI following non-surgical treatment.

Purpose: In order to estimate clinical effects of Oriental Medicine Treatment with acupotomy therapy of Peroneal nerve Palsy. Methods: From 10th June, 2010 to 19th June, 2010, 1 female patient diagnosed as Peroneal nerve Palsy(clinical diagnosed) was treated with general oriental medicine therapy (acupuncture, pharmacopuncture,moxibustion, cupping, physical therapy, herbal medication) and acupotomy. Results: The patient's left foot drop was remarkably improved. Conclusions: This study demonstrates that oriental medical treatment with acuputomy therapy has notable effect in improving symptoms of peroneal nerve palsy. as though we had not wide experience in this treatment, more research is needed.

Objectives : This study was to investigate the effects of Oriental medical treatment on ALS. Methods : We investigated 12 ALS patients which were admitted to Gwang-Ju O.M.hospital for 3 months and follow-up at 8 months after discharge. All patients were treated by SAAM-acupuncture, herb medication, Bee venom Pharmacopuncture therapy, Needle-embedding therapy, etc and after discharge self-therapy at home. We evaluated patients using the Amyotrophic lateral sclerosis Functional Rating Scale-Revised(ALSFRS-R), Medical Research Council (MRC) Scale. Results : After 1 month, mean ALSFRS-R score of patients was 29.08±7.99, 2 months 28.70±7.17, 3months 28.16±8.23, 1 year 21.33±9.93 and mean MRC Scale of patients was 25.34±8.45, 2 months 25.34±8.45, 3months 21.56±9.20. But in both cases, the variation was not statistically significant. Conclusions : We think that the results of this case be a pilot study that proves the effect of Oriental Medical treatment on ALS.

Purpose : In order to estimate clinical effects of Oriental Medicine Treatment with acupotomy therapy of Tarsal tunnel Syndrome Methods : From 5th November, 2008 to 8th November, 2008, 1 male patient diagnosed as Tarsal tunnel syndrome(clinical diagnosed) was treated with general oriental medicine therapy (acupuncture, moxibustion, cupping, physical therapy, herbal medication) and acupotomy. Results : The patient's Rt foot paresthesia, pain were remarkably improved. Conclusions : This study demonstrates that oriental medical treatment with acuputomy therapy has notable effect in improving symptoms of tarsal tunnel syndrome. as though we had not wide experience in this treatment, more research is needed.

Abstract Background Reduced gas transfer in patients with pulmonary arterial hypertension (PAH) is traditionally attributed to remodeling and progressive loss of pulmonary arterial vasculature that results in decreased capillary blood volume available for gas exchange. Methods We tested this hypothesis by determination of lung diffusing capacity (DL) and its components, the alveolar capillary membrane diffusing capacity (Dm) and lung capillary blood volume (Vc) in 28 individuals with PAH in comparison to 41 healthy individuals, and in 19 PAH patients over time. Using single breath simultaneous measure of diffusion of carbon monoxide (DLCO) and nitric oxide (DLNO), DL and Dm were respectively determined, and Vc calculated. Dm and Vc were evaluated over time in relation to standard clinical indicators of disease severity, including brain natriuretic peptide (BNP), 6-minute walk distance (6MWD) and right ventricular systolic pressure (RVSP) by echocardiography. Results Both DLCO and DLNO were reduced in PAH as compared to controls and the lower DL in PAH was due to loss of both Dm and Vc (all p CO of PAH patients did not change over time, DLNO decreased by 24 ml/min/mmHg/year (p = 0.01). Consequently, Dm decreased and Vc tended to increase over time, which led to deterioration of the Dm/Vc ratio, a measure of alveolar-capillary membrane functional efficiency without changes in clinical markers. Conclusions The findings indicate that lower than normal gas transfer in PAH is due to loss of both Dm and Vc, but that deterioration of Dm/Vc over time is related to worsening membrane diffusion.

Abstract Diabetic patients who attempt strict management of blood glucose levels frequently experience hypoglycemia. Severe and prolonged hypoglycemia causes neuronal death and cognitive impairment. There is no effective tool for prevention of these unwanted clinical sequelae. Minocycline, a second-generation tetracycline derivative, has been recognized as an anti-inflammatory and neuroprotective agent in several animal models such as stroke and traumatic brain injury. In the present study, we tested whether minocycline also has protective effects on hypoglycemia-induced neuronal death and cognitive impairment. To test our hypothesis we used an animal model of insulin-induced acute hypoglycemia. Minocycline was injected intraperitoneally at 6 hours after hypoglycemia/glucose reperfusion and injected once per day for the following 1 week. Histological evaluation for neuronal death and microglial activation was performed from 1 day to 1 week after hypoglycemia. Cognitive evaluation was conducted 6 weeks after hypoglycemia. Microglial activation began to be evident in the hippocampal area at 1 day after hypoglycemia and persisted for 1 week. Minocycline injection significantly reduced hypoglycemia-induced microglial activation and myeloperoxidase (MPO) immunoreactivity. Neuronal death was significantly reduced by minocycline treatment when evaluated at 1 week after hypoglycemia. Hypoglycemia-induced cognitive impairment is also significantly prevented by the same minocycline regimen when subjects were evaluated at 6 weeks after hypoglycemia. Therefore, these results suggest that delayed treatment (6 hours post-insult) with minocycline protects against microglial activation, neuronal death and cognitive impairment caused by severe hypoglycemia. The present study suggests that minocycline has therapeutic potential to prevent hypoglycemia-induced brain injury in diabetic patients.

Abstract Background We recently have shown that Charged multivesicular protein/Chromatin modifying protein1A (Chmp1A) functions as a tumor suppressor in human pancreatic tumor cells. Pancreatic cancer has the worst prognosis of all cancers with a dismal 5-year survival rate. Preclinical studies using ATRA for treating human pancreatic cancer suggest this compound might be useful for treatment of pancreatic cancer patients. However, the molecular mechanism by which ATRA inhibits growth of pancreatic cancer cells is not clear. The objective of our study was to investigate whether Chmp1A is involved in ATRA-mediated growth inhibition of human pancreatic tumor cells. Results We performed microarray studies using HEK 293T cells and discovered that Chmp1A positively regulated Cellular retinol-binding protein 1 (CRBP-1). CRBP-1 is a key regulator of All-trans retinoic acid (ATRA) through ATRA metabolism and nuclear localization. Since our microarray data indicates a potential involvement of Chmp1A in ATRA signaling, we tested this hypothesis by treating pancreatic tumor cells with ATRA in vitro. In the ATRA-responsive cell lines, ATRA significantly increased the protein expression of Chmp1A, CRBP-1, P53 and phospho-P53 at serine 15 and 37 position. We found that knockdown of Chmp1A via shRNA abolished the ATRA-mediated growth inhibition of PanC-1 cells. Also, Chmp1A silencing diminished the increase of Chmp1A, P53 and phospho-P53 protein expression induced by ATRA. In the ATRA non-responsive cells, ATRA did not have any effect on the protein level of Chmp1A and P53. Chmp1A over-expression, however, induced growth inhibition of ATRA non-responsive cells, which was accompanied by an increase of Chmp1A, P53 and phospho-P53. Interestingly, in ATRA responsive cells Chmp1A is localized to the nucleus, which became robust upon ATRA treatment. In the ATRA-non-responsive cells, Chmp1A was mainly translocated to the plasma membrane upon ATRA treatment. Conclusion Collectively our data provides evidence that Chmp1A mediates the growth inhibitory activity of ATRA in human pancreatic cancer cells via regulation of CRBP-1. Our results also suggest that nuclear localization of Chmp1A is important in mediating ATRA signaling.

Orientia tsutsugamushi a causal agent of scrub typhus, is an obligate intracellular bacterium that, akin to other rickettsiae, is dependent on host cell-derived nutrients for survival and thus pathogenesis. Based on limited experimental evidence and genome-based in silico predictions, O. tsutsugamushi is hypothesized to parasitize host central carbon metabolism (CCM). Here, we (re-)evaluated O. tsutsugamushi dependency on host cell CCM as initiated by glucose and glutamine. Orientia infection had no effect on host glucose and glutamine consumption or lactate accumulation, indicating no change in overall flux through CCM. However, host cell mitochondrial activity and ATP levels were reduced during infection and correspond with lower intracellular glutamine and glutamate pools. To further probe the essentiality of host CCM in O. tsutsugamushi proliferation, we developed a minimal medium for host cell cultivation and paired it with chemical inhibitors to restrict the intermediates and processes related to glucose and glutamine metabolism. These conditions failed to negatively impact O. tsutsugamushi intracellular growth, suggesting the bacterium is adept at scavenging from host CCM. Accordingly, untargeted metabolomics was utilized to evaluate minor changes in host CCM metabolic intermediates across O. tsutsugamushi infection and revealed that pathogen proliferation corresponds with reductions in critical CCM building blocks, including amino acids and TCA cycle intermediates, as well as increases in lipid catabolism. This study directly correlates O. tsutsugamushi proliferation to alterations in host CCM and identifies metabolic intermediates that are likely critical for pathogen fitness.IMPORTANCEObligate intracellular bacterial pathogens have evolved strategies to reside and proliferate within the eukaryotic intracellular environment. At the crux of this parasitism is the balance between host and pathogen metabolic requirements. The physiological basis driving O. tsutsugamushi dependency on its mammalian host remains undefined. By evaluating alterations in host metabolism during O. tsutsugamushi proliferation, we discovered that bacterial growth is independent of the host's nutritional environment but appears dependent on host gluconeogenic substrates, including amino acids. Given that O. tsutsugamushi replication is essential for its virulence, this study provides experimental evidence for the first time in the post-genomic era of metabolic intermediates potentially parasitized by a scrub typhus agent., Competing Interests: The authors declare no conflict of interest.

The turbulent ocean surface boundary layer is a key part of the climate system affecting both the energy and carbon cycles. Accurately simulating the boundary layer is critical in improving climate model performance, which deeply relies on our understanding of the turbulence in the boundary layer. Turbulent energy sources in the boundary layer are traditionally believed to be dominated by waves, winds and convection. Recently, submesoscale phenomena with spatial scales of 0.1~10 km at ocean fronts have been shown to also make a contribution. Here, by applying a non-dimensional turbulent kinetic energy budget equation, we show that the submesoscale geostrophic shear production at fronts is a significant turbulent energy source within the ocean boundary layer away from the sea surface. The contribution reaches 34% of the total dissipation in winter and 17% in summer at the mid-depth of the boundary layer, despite its intermittency in space and time. This work indicates fundamental deficiencies in previous conceptions of ocean boundary layer turbulence, and invites a reappraisal of the sampling scale in observations, model resolution and parameterizations, and other consequences of the global energy budget., (© 2024. The Author(s).)

Background: Beta-lactams are the most common antibiotic class reported to cause allergic drug reactions. Previous literature suggests an increased prevalence of penicillin drug allergy in female patients in both inpatient and outpatient settings. However, the effects of sex and gender have not been well characterized regarding the entire class of beta-lactam antibiotics., Objective: This systematic review and meta-analysis aimed to identify sex and gender-based differences in the prevalence of immediate beta-lactam allergy., Methods: We performed an electronic search of Ovid MEDLINE/PubMed, Embase, Web of Science, Scopus, and the Cochrane Library between 2013-2023. Patients with a documented beta-lactam allergy who underwent allergy testing with skin testing, oral drug challenge, or serum-specific IgE were included. We quantitatively assessed sex- and gender-based differences in beta-lactam allergy with meta-analysis., Results: We included 69 primary studies, assessing 53,989 participants from outpatient and inpatient cohorts. 7,558 patients had a confirmed beta-lactam allergy. There was no difference in the prevalence of positive beta-lactam allergy test between males and females. Sub-group analysis of studies that performed oral challenges did show a higher risk of beta-lactam allergy in females than males (RR 1.40, 95% CI 1.18-1.66, p < 0.001, I 2 =77.8%). Finally, there was a higher proportion of females (64.8%) than males enrolled in beta-lactam allergy studies., Conclusions: Our findings suggest both sex-based and gender-based differences in the prevalence of immediate beta-lactam allergy. Both biological factors, such as sex hormones, and gender-based behaviors, including increased healthcare utilization, may contribute to higher rates of beta-lactam allergy diagnosis in females., (Copyright © 2024. Published by Elsevier Inc.)

Flood risk has become a major concern in many regions due to socio-economic growth and rising water levels. In this paper, we introduce a real options model that integrates the Generalized Additive Models for Location, Scale, and Shape framework with Extreme Value Theory to evaluate adaptation measures for flood risk management. Our model allows for uncertain water level rise, climate indices and growing loss exposure. In a case study of flood risk management for New York City, we find that while immediate investment in a barrier and dike project can provide a substantial net present value ($10.96 billion), investing at the optimal time can significantly improve the investment value by 54.84%. Our sensitivity analysis suggests that discount rate is the most important parameter, followed by the mean level of water rise and the water level rise uncertainty. We also find that investment delay is longer when the discount rate or the water level rise uncertainty is higher or when the expected water level rise is lower., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Chi Truong reports financial support was provided by Society of Actuaries, the United States. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Avian primordial germ cells (PGCs) are important culture cells for the production of transgenic chickens and preservation of the genetic resources of endangered species; however, culturing these cells in vitro proves challenging. Although the proliferation of chicken PGCs is dependent on insulin, the underlying molecular mechanisms remain unclear. In the present study, we explored the expression of the PI3K/AKT signaling pathway in PGCs, investigated its effects on PGC self-renewal and biological properties, and identified the underlying mechanisms. Our findings indicated that although supplementation with the PI3K/AKT activator IGF-1 failed to promote proliferation under the assessed culture conditions, the PI3K/AKT inhibitor LY294002 resulted in retarded cell proliferation and reduced expression of germ cell-related markers. We further demonstrated that inhibition of PI3K/AKT regulates the cell cycle and promotes apoptosis in PGCs by activating the expression of BAX and inhibiting that of Bcl-2. These findings indicated that the PI3K/AKT pathway is required for cell renewal, apoptosis, and maintenance of the reproductive potential in chicken PGCs. This study aimed to provide a theoretical basis for the optimization and improvement of a culture system for chicken PGCs and provide insights into the self-renewal of vertebrate PGCs as well as potential evolutionary changes in this unique cell population., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Hemorrhagic fever with renal syndrome (HFRS) is caused by hantaviruses. Data of 34 patients with HFRS hospitalized at Chosun University Hospital, South Korea, between 2010 and 2021 were retrospectively analyzed. Nested reverse transcription polymerase chain reaction (RT-nPCR) targeting the L segment of hantavirus and sequencing were used for diagnosis. Most cases occurred in men and during the months of October through December. Common symptoms were fever, chills, gastrointestinal symptoms, and myalgia. The common laboratory abnormalities were thrombocytopenia, proteinuria, and elevated levels of serum creatinine, aspartate transaminase, alanine transaminase, and lactate dehydrogenase. Approximately 91.2% of patients had the Hantaan virus with a new genotype cluster, whereas 8.8% had the Seoul virus. Seropositivity based on IgM titer >1:32 on admission was noted in 20.6%, and a 4-fold increase in IgG titer of 1:512 was observed in 11.8%. This study demonstrated that RT-nPCR targeting the L segment of hantaviruses is a more reliable diagnostic method compared to serological testing.

Objective: The current study aimed to investigate the effect of dietary supplementation of xylanase alone or combination of xylanase and β-glucanase in high non-starch polysaccharides (NSP) diets with low energy on growth performance, meat quality, intestinal measurements, stress responses, and energy and nutrient utilization in broiler chickens., Methods: A total of four hundred 8-d-old Ross 308 broiler chickens were randomly allotted to 1 of 4 treatment groups with 10 replicates. A positive control (PC) diet was formulated with adequate energy and nutrients, whereas a negative control (NC) diet had 100 kcal/kg less AMEn than the PC diet with increasing inclusion of high NSP ingredients. Two additional diets were produced by supplementing 0.1% xylanase alone or 0.1% xylanase and β-glucanase mixture in the NC diet. Experiments lasted for 27 d., Results: Birds fed PC diets had less (p<0.05) FCR than those fed NC diets. Birds fed NC diets supplemented with xylanase alone or combination of xylanase and β-glucanase had less (p<0.05) FCR than those fed NC diets. Dietary supplementation of xylanase alone in NC diets exhibited the highest (p<0.05) breast meat pH among dietary treatments. Birds fed PC diets or NC diets supplemented with xylanase and β-glucanase combination exhibited greater (p<0.05) VH:CD ratio than those fed NC diets. Dietary supplementation of xylanase alone and combination of xylanase and β-glucanase in NC diets decreased (p<0.05) ileal digesta viscosity and increased (p<0.05) xylo-oligosaccharide concentrations in the gastrointestinal tract (GIT) compared with NC diets without affecting energy and nutrient utilization in NC diets., Conclusion: Dietary supplementation of xylanase in high NSP diets with low energy concentrations improves growth performance by decreasing digesta viscosity and increasing concentrations of xylo-oligosaccharides in the GIT of broiler chickens. However, little additional benefits of β-glucanase supplementation in combination with xylanase are identified for broiler chickens.

Ultraviolet photodissociation (UVPD) has been shown to be a versatile ion activation strategy for the characterization of peptides and intact proteins among other classes of biological molecules. Combining the high-performance mass spectrometry (MS/MS) capabilities of UVPD with the high-resolution separation of trapped ion mobility spectrometry (TIMS) presents an opportunity for enhanced structural elucidation of biological molecules. In the present work, we integrate a 193 nm excimer laser in a TIMS-time-of-flight (TIMS-TOF) mass spectrometer for UVPD in the collision cell and use it for the analysis of several mass-mobility-selected species of ubiquitin and myoglobin. The resultant data displayed differences in fragmentation that could be correlated with changes in protein conformation. Additionally, this mobility-resolved UVPD strategy was applied to collision-induced unfolded ions of ubiquitin to follow changes in fragmentation patterns relating to the extent of protein unfolding. This platform and methodology offer new opportunities for exploring how conformational variations are manifested in the fragmentation patterns of gas-phase ions.

Background: There are marked sex differences in the prevalence and severity of asthma, both during childhood and adulthood. There is a relative lack of comprehensive studies exploring sexdifferences in pediatric asthma cohorts., Objective: To identify the most relevant sex differences in sociodemographic, clinical, and laboratory variables in a well-characterized large pediatric asthma cohort., Methods: We performed a cross-sectional analysis of the Mayo Clinic Olmsted County Birth Cohort. In the full birth cohort, we used a natural language-processing algorithm based on the Predetermined Asthma Criteria for asthma ascertainment. In a stratified random sample of 300 children, we obtained additional pulmonary function tests and laboratory data. We identified the significant sex differences among available sociodemographic, clinical, and laboratory variables., Results: Boys were more frequently diagnosed with having asthma than girls and were younger at the time of asthma diagnosis. There were no sex differences in relation to socioeconomic status. We identified a male predominance in the presence of a tympanostomy tube and a female predominance in the history of pneumonia. A higher percentage of boys had a forced expiratory volume in 1 second/forced vital capacity ratio less than 0.85. Blood eosinophilia and atopic sensitization were also more common in boys. Finally, boys had higher levels of serum periostin than girls., Conclusion: This study described significant sex differences in a large pediatric asthma cohort. Overall, boys had earlier and more severe asthma than girls. Differences in blood eosinophilia and serum periostin provide insights into possible mechanisms of the sex bias in childhood asthma., Competing Interests: Disclosures The authors have no conflicts of interest to report., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Study Objective: Improved understanding of factors affecting prolonged emergency department (ED) length of stay is crucial to improving patient outcomes. Our investigation builds on prior work by considering ED length of stay in operationally distinct time periods and using benchmark and novel machine learning techniques applied only to data that would be available to ED operators in real time., Methods: This study was a retrospective review of patient visits over 1 year at 2 urban EDs, including 1 academic and 1 academically affiliated ED, and 2 suburban, community EDs. ED length of stay was partitioned into 3 components: arrival-to-room, room-to-disposition, and admit disposition to departure. Prolonged length of stay for each component was considered beyond 1, 3, and 2 hours, respectively. Classification models (logistic regression, random forest, and XGBoost) were applied, and important features were evaluated., Results: In total, 135,044 unique patient encounters were evaluated for the arrival-to-room, room-to-disposition, and admit disposition-to-departure models, which had accuracy ranges of 84% to 96%, 66% to 77%, and 62% to 72%, respectively. Waiting room and ED volumes were important features in all arrival-to-room models. Room-to-disposition results identified patient characteristics and ED volume as the most important features for prediction. Boarder volume was an important feature of the admit disposition-to-departure models for all sites. Academic site models noted nurse staffing ratios as important, whereas community site models noted hospital capacity and surgical volume as important for admit disposition-to-departure prediction., Conclusion: This study identified granular capacity, flow, and nurse staffing predictors of ED length of stay not previously reported in the literature. Our novel methodology allowed for more accurate and operationally meaningful findings compared to prior modeling methods., (Copyright © 2024 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

The growing prevalence of artificial intelligence (AI) in our lives has brought the impact of AI-based decisions on human judgments to the forefront of academic scholarship and public debate. Despite growth in research on people's receptivity towards AI, little is known about how interacting with AI shapes subsequent interactions among people. We explore this question in the context of unfair decisions determined by AI versus humans and focus on the spillover effects of experiencing such decisions on the propensity to act prosocially. Four experiments (combined N = 2425) show that receiving an unfair allocation by an AI (versus a human) actor leads to lower rates of prosocial behavior towards other humans in a subsequent decision-an effect we term AI-induced indifference. In Experiment 1, after receiving an unfair monetary allocation by an AI (versus a human) actor, people were less likely to act prosocially, defined as punishing an unfair human actor at a personal cost in a subsequent, unrelated decision. Experiments 2a and 2b provide evidence for the underlying mechanism: People blame AI actors less than their human counterparts for unfair behavior, decreasing people's desire to subsequently sanction injustice by punishing the unfair actor. In an incentive-compatible design, Experiment 3 shows that AI-induced indifference manifests even when the initial unfair decision and subsequent interaction occur in different contexts. These findings illustrate the spillover effect of human-AI interaction on human-to-human interactions and suggest that interacting with unfair AI may desensitize people to the bad behavior of others, reducing their likelihood to act prosocially. Implications for future research are discussed. All preregistrations, data, code, statistical outputs, stimuli qsf files, and the Supplementary Appendix are posted on OSF at: https://bit.ly/OSF&#95;unfairAI., (Copyright © 2024. Published by Elsevier B.V.)

Background: HIV self-testing (HIVST) offers an innovative and promising approach to increasing HIV testing among Black men in the United States, a population disproportionately affected by HIV. However, engaging Black men in traditional HIV prevention programs has been challenging due to stigma, medical mistrust, and limited access to preventive health services. This formative qualitative study aimed to explore the potential of utilizing barbershops as an example of a nontraditional healthcare venue to promote and distribute HIVST., Methods: Four virtual focus group discussions (FGDs) consisting of 19 participants in North Carolina were conducted with Black men, including barbershop business owners, barbers, and their customers, to assess perceptions of HIVST and the acceptability of partnering with barbershop businesses to promote HIVST. FGDs were digitally recorded, transcribed, and analyzed using a deductive coding approach to thematic analysis., Results: Participants reported that the trusting relationship between barbers and their customers, which may not exist between Black men and health care providers, is a facilitator of collaborating with barbershop businesses to reach Black men for HIVST distribution. Participants recommended providing education for barbers on the use of HIVST, as well as how to inform self-testers about linkage to care following HIVST to build the credibility of the barbers in delivering the intervention. Participants also raised the issue of the cost of HIVST to barbershop customers as a potential barrier to implementation, as well as the possibility that the implementation of such interventions could be seen as out of place in a barbershop business venue. Participants also expressed a strong belief that compensation to barbershops and their employees should accompany any intervention., Conclusion: These findings suggest that barbershop business venues may provide an appropriate venue for HIVST promotion and distribution, though factors like cost, training, and incentivization of implementers are necessary to consider in implementation planning. Furthermore, partnerships between public health actors and the business community must be built on equitable engagement to ensure the long-term viability of these critical initiatives., (© 2024. The Author(s).)

The amino acid position within a histone sequence and the chemical nature of post-translational modifications (PTMs) are essential for elucidating the "Histone Code". Previous work has shown that PTMs induce specific biological responses and are good candidates as biomarkers for diagnostics. Here, we evaluate the analytical advantages of trapped ion mobility (TIMS) with parallel accumulation-serial fragmentation (PASEF) and tandem mass spectrometry (MS/MS) for bottom-up proteomics of model cancer cells. The study also considered the use of nanoliquid chromatography (LC) and traditional methods: LC-TIMS-PASEF-ToF MS/MS vs nLC-TIMS-PASEF-ToF MS/MS vs nLC-MS/MS. The addition of TIMS and PASEF-MS/MS increased the number of detected peptides due to the added separation dimension. All three methods showed high reproducibility and low RSD in the MS domain (<5 ppm). While the LC, nLC and TIMS separations showed small RSD across samples, the accurate mobility (1/K 0 ) measurements (<0.6% RSD) increased the confidence of peptide assignments. Trends were observed in the retention time and mobility concerning the number and type of PTMs (e.g., ac, me 1-3 ) and their corresponding unmodified, propionylated peptide that aided in peptide assignment. Mobility separation permitted the annotation of coeluting structural and positional isomers and compared with nLC-MS/MS showed several advantages due to reduced chemical noise.

Lipids are highly diverse, and small changes in lipid structures and composition can have profound effects on critical biological functions. Stable isotope labeling (SIL) offers several advantages for the study of lipid distribution, mobilization, and metabolism, as well as de novo lipid synthesis. The successful implementation of the SIL technique requires the removal of interferences from endogenous molecules. In the present work, we describe a high-throughput analytical protocol for the screening of SIL lipids from biological samples; examples will be shown of lipid de novo identification during mosquito ovary development. The use of complementary liquid chromatography trapped ion mobility spectrometry and mass spectrometry allows for the separation and lipids assignment from a single sample in a single scan (<1 h). The described approach takes advantage of recent developments in data-dependent acquisition and data-independent acquisition, using parallel accumulation in the mobility trap followed by sequential fragmentation and collision-induced dissociation. The measurement of SIL at the fatty acid chain level reveals changes in lipid dynamics during the ovary development of mosquitoes. The lipids de novo structures are confidently assigned based on their retention time, mobility, and fragmentation pattern.

Ultrasound elastography has been available on most modern systems; however, the implementation of quality processes tends to be ad hoc. It is essential for a medical physicist to benchmark elastography measurements on each system and track them over time, especially after major software upgrades or repairs. This study aims to establish baseline data using phantoms and monitor them for quality assurance in elastography. In this paper, we utilized two phantoms: a set of cylinders, each with a composite material with varying Young's moduli, and an anthropomorphic abdominal phantom containing a liver modeled to represent early-stage fibrosis. These phantoms were imaged using three ultrasound manufacturers' elastography functions with either point or 2D elastography. The abdominal phantom was also imaged using magnetic resonance elastography (MRE) as it is recognized as the non-invasive gold standard for staging liver fibrosis. The scaling factor was determined based on the data acquired using MR and US elastography from the same vendor. The ultrasound elastography measurements showed inconsistency between different manufacturers, but within the same manufacturer, the measurements showed high repeatability. In conclusion, we have established baseline data for quality assurance procedures and specified the criteria for the acceptable range in liver fibrosis phantoms during routine testing.

Introduction: Cancer-associated cachexia (CC) is a progressive syndrome characterized by unintentional weight loss, muscle atrophy, fatigue, and poor outcomes that affects most patients with pancreatic ductal adenocarcinoma (PDAC). The ability to identify and classify CC stage along its continuum early in the disease process is challenging but critical for management., Objectives: The main objective of this study was to determine the prevalence of CC stage overall and by sex and race and ethnicity among treatment-naïve PDAC cases using clinical, nutritional, and functional criteria. Secondary objectives included identifying the prevalence and predictors of higher symptom burden, supportive care needs, and quality of life (QoL), and examining their influence on overall survival (OS)., Materials and Methods: A population-based multi-institutional prospective cohort study of patients with PDAC was conducted between 2018 and 2021 by the Florida Pancreas Collaborative. Leveraging patient-reported data and laboratory values, participants were classified at baseline into four stages [non-cachexia (NCa), pre-cachexia (PCa), cachexia (Ca), and refractory cachexia (RCa)]. Multivariate regression, Kaplan Meier analyses, and Cox regression were conducted to evaluate associations., Results: CC stage was estimated for 309 PDAC cases (156 females, 153 males). The overall prevalence of NCa, PCa, Ca, and RCa was 12.9%, 24.6%, 54.1%, and 8.4%, respectively. CC prevalence across all CC stages was highest for males and racial and ethnic minorities. Criteria differentiated NCa cases from other groups, but did not distinguish PCa from Ca. The most frequently reported symptoms included weight loss, fatigue, pain, anxiety, and depression, with pain significantly worsening over time. The greatest supportive care needs included emotional and physical domains. Males, Black people, and those with RCa had the worst OS., Conclusions: Using clinical, nutritional, and functional criteria, nearly one-quarter of the PDAC cases in our diverse, multi-institutional cohort had PCa and 62.5% had Ca or RCa at the time of diagnosis. The PCa estimate is higher than that reported in prior studies. We recommend these criteria be used to aid in CC classification, monitoring, and management of all incident PDAC cases. Findings also highlight the recommendation for continued emotional support, assistance in alleviating pain, and supportive care needs throughout the PDAC treatment journey., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Permuth, Park, Chen, Basinski, Powers, Gwede, Dezsi, Gomez, Vyas, Biachi, Cortizas, Crowder, Genilo-Delgado, Green, Greene, Gregg, Hoffe, Jiang, Kim, Vasudevan, Garcialopez De Llano, Menon, Mo, MorenoUrazan, Mok, Parker, Rajasekhara, Rasool, Sinnamon, Sparks, Stewart, Tardif, Tassielli, Teer, Tran, Turner, Vadaparampil, Whelan, Douglas, Velanovich, Karachristos, Legaspi, Meredith, Molina-Vega, Huguet, Arnoletti, Bloomston, Trevino, Merchant, Pimiento, Hodul, Malafa, Fleming, Judge, Jeong and Judge.)

Objectives: Much has been written about the utility of genomic databases to public health. Within food safety these databases contain data from two types of isolates-those from patients (i.e., clinical) and those from non-clinical sources (e.g., a food manufacturing environment). A genetic match between isolates from these sources represents a signal of interest. We investigate the match rate within three large genomic databases (Listeria monocytogenes, Escherichia coli, and Salmonella) and the smaller Cronobacter database; the databases are part of the Pathogen Detection project at NCBI (National Center for Biotechnology Information)., Results: Currently, the match rate of clinical isolates to non-clinical isolates is 33% for L. monocytogenes, 46% for Salmonella, and 7% for E. coli. These match rates are associated with several database features including the diversity of the organism, the database size, and the proportion of non-clinical BioSamples. Modeling match rate via logistic regression showed relatively good performance. Our prediction model illustrates the importance of populating databases with non-clinical isolates to better identify a match for clinical samples. Such information should help public health officials prioritize surveillance strategies and show the critical need to populate fledgling databases (e.g., Cronobacter sakazakii)., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Mass-spectrometry based assays in structural biology studies measure either intact or digested proteins. Typically, different mass spectrometers are dedicated for such measurements: those optimized for rapid analysis of peptides or those designed for high molecular weight analysis. A commercial trapped ion mobility-quadrupole-time-of-flight (TIMS-Q-TOF) platform is widely utilized for proteomics and metabolomics, with ion mobility providing a separation dimension in addition to liquid chromatography. The ability to perform high-quality native mass spectrometry of protein complexes, however, remains largely uninvestigated. Here, we evaluate a commercial TIMS-Q-TOF platform for analyzing noncovalent protein complexes by utilizing the instrument's full range of ion mobility, MS, and MS/MS (both in-source activation and collision cell CID) capabilities. The TIMS analyzer is able to be tuned gently to yield collision cross sections of native-like complexes comparable to those previously reported on various instrument platforms. In-source activation and collision cell CID were robust for both small and large complexes. TIMS-CID was performed on protein complexes streptavidin (53 kDa), avidin (68 kDa), and cholera toxin B (CTB, 58 kDa). Complexes pyruvate kinase (237 kDa) and GroEL (801 kDa) were beyond the trapping capabilities of the commercial TIMS analyzer, but TOF mass spectra could be acquired. The presented results indicate that the commercial TIMS-Q-TOF platform can be used for both omics and native mass spectrometry applications; however, modifications to the commercial RF drivers for both the TIMS analyzer and quadrupole (currently limited to m / z 3000) are necessary to mobility analyze protein complexes greater than about 60 kDa.